Several hundred different known viruses infect humans and animals. Viruses that infect humans and animals often spread via respiratory and enteric excretions. For example, enterovirus 71 (EV71) is a single stranded, RNA virus of the genus Enterovirus in the family Picornaviridae. It is classified genetically into 3 groups (A, B and C) and 11 genotypes (A, B1-B5, C1-C5). EV71 comprises four major capsid proteins such as VP1, VP2, VP3 and VP4. Of these, VP1 is thought to be mainly responsible for the attachment of virus to target cells and hence harbours the main antigenic determinant for virus neutralization. Indeed, immunological studies with different enterovirus strains have indicated that the dominant epitopes of several neutralizing mAbs are located on VP1. EV71 is one virus responsible for hand foot and mouth disease.
Hand foot and mouth disease has become a major emerging infectious disease and is an important threat especially in Asia. A large outbreak of HFMD due to EV71 infection occurred in Taiwan in 1998, including 129,106 case reports, 405 children with severe complications, and more than 80 deaths. Since 1997, EV71 infection has taken on new significance, with increasing numbers of cases. Episodes caused by various strains of EV71 have continued to reappear in other countries such as Thailand, China and Vietnam. The expanding geographic distribution of EV71 infections with recent outbreaks in Singapore indicates that more human populations are at risk. Conventional EV71 vaccines are based on inactivated viruses which are produced in cell lines and inactivated by chemical means. However, the virulent nature of the virus requires that the viruses be handled under biosafety level conditions, thus the production of vaccines candidates using conventional techniques would require significant changes in current manufacturing procedures that might delay vaccine production in case of the outbreak.
Formalin-inactivated and live attenuated vaccines in controlling epidemic poliomyelitis and in the eradication of poliovirus highlights the potential for control of EV71 epidemics by mass vaccination. Based on this formalin-inactivated EV71 vaccine was developed in response to Bulgarian epidemic in 1975 but was not used to control the epidemic and has not been used since. Furthermore no data on the efficacy of the Bulgarian vaccine are available.
A good vaccine effective for protection against viral infections, such as EV71 is therefore highly desirable.